Early-to-mid stage idiopathic Parkinson’s disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females
-
Published:2023-11-20
Issue:1
Volume:14
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Capelle Christophe M., Ciré SéverineORCID, Hedin Fanny, Hansen Maxime, Pavelka Lukas, Grzyb KamilORCID, Kyriakis DimitriosORCID, Hunewald OliverORCID, Konstantinou Maria, Revets Dominique, Tslaf VeraORCID, Marques Tainá M.ORCID, Gomes Clarissa P. C.ORCID, Baron Alexandre, Domingues Olivia, Gomez Mario, Zeng NiORCID, Betsou Fay, May PatrickORCID, Skupin AlexanderORCID, Cosma AntonioORCID, Balling RudiORCID, Krüger Rejko, Ollert MarkusORCID, Hefeng Feng Q.ORCID
Abstract
AbstractNeuroinflammation in the brain contributes to the pathogenesis of Parkinson’s disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments.
Funder
Fonds National de la Recherche Luxembourg Integrated BioBank of Luxembourg
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference123 articles.
1. Dorsey, E. R. et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68, 384–386 (2007). 2. Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Prim. 3, 17013 (2017). 3. Wang, Q., Liu, Y. & Zhou, J. Neuroinflammation in Parkinson’s disease and its potential as therapeutic target. Transl. Neurodegener. 4, 19 (2015). 4. Qin, X. Y., Zhang, S. P., Cao, C., Loh, Y. P. & Cheng, Y. Aberrations in peripheral inflammatory cytokine levels in Parkinson disease: a systematic review and meta-analysis. JAMA Neurol. 73, 1316–1324 (2016). 5. Reale, M. et al. “Peripheral cytokines profile in Parkinson’s disease. Brain Behav. Immun. 23, 55–63 (2009).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|